The primary goal of the application is to examine changes in synaptic activity that occur during withdrawal and following cocaine primed reinstatement, and seeks to provide further insight into molecular and cellular alterations that underlie addiction. The studies outlined within the application will use electrophysiology to examine our hypotheses. Specifically, Aim 1 will characterize the physiological response of populations of neurons in the nucleus accumbens to prefrontal cortical stimulation. The goal of Aim 2 is to determine the role of cystine/glutamate exchange and group II metabotropic glutamate receptors in mediating synaptic transmission during withdrawal and following a cocaine priming injection. Rats will be trained to self administer cocaine and undergo a 14-21 day withdrawal period. A different group of rats will act yoked saline controls. At the end of the withdrawal period, mPFC glutamatergic efferents will be stimulated and field recordings measured in the core of the nucleus accumbens.